-deficient mutant contributes to bacterial virulence through enhancing the PhoB-mediated pathway in response to host environment.

Unlabelled: is a major opportunistic pathogen that causes lung infections in patients with cystic fibrosis and chronic obstructive pulmonary disease. Loss-of-function mutations in the quorum-sensing regulatory gene commonly arise during chronic infections, which are associated with exaggerated inflammation and accelerated decline in lung function. Here, in a murine cutaneous abscess model, infection with a Δ mutant or a wild-type-Δ mutant-mixed population resulted in higher bacterial loads and more severe tissue damage than infection by the wild-type strain.

Evolution of Resistant Mutants in Persister Cells Under Meropenem Treatment.

Bacterial persisters are dormant cells that survive antibiotic treatment, serving as a reservoir for the emergence of resistant mutations. The evolution of antibiotic resistance poses a significant challenge to public health. In this study, we investigated the development of resistance in persister cells by exposing the reference strain PA14 to meropenem and tracked the emergence of resistance mutations over serial passages.

The fatty acid synthesis gene affects lipopolysaccharide synthesis and colistin susceptibility in .

Unlabelled: Bacterial metabolism impacts susceptibility to antibiotics. Here, we found that mutation of the fatty acid response regulator gene pvrA decreases bacterial susceptibility to colistin. The fatty acid synthesis gene is upregulated in the mutant.

Elongation factor-G1A identified as a novel effector protein translocated into cells and a key modulator of Pseudomonas aeruginosa physiology and host cellular responses.

Pseudomonas aeruginosa has two closely related elongation factors, EF-G1A and EF-G1B, which share 90 % sequence similarity. Despite their high sequence homology, the role of EF-G in P. aeruginosa pathogenesis remains not fully understood.

A universal aggregation-induced emission probe for dialkylaminoethylthiols to determine V-type nerve agents.

An aggregation-induced emission (AIE) probe, 4-(1,2,2-triphenylvinyl)phenyl acrylate (TPE-ACY), has been developed for the prompt determination of VX, one of the most dangerous chemical warfare agents. This probe contains a tetraphenylethene unit and an α, β-unsaturated ester unit as the recognition site for diisopropylaminoethylthiol (DISH), the P-S bond hydrolysis product or the key precursor of VX. TPE-ACY exhibits rapid fluorescence response to DISH with a low limit of detection of 0.

Azithromycin represses evolution of ceftazidime/avibactam resistance by translational repression of in .

Antibiotic combinations can slow down resistance development and/or achieve synergistic therapeutic effects. In this study, we observed that a combined use of ceftazidime-avibactam (CZA) with azithromycin effectively repressed CZA resistance development in . Transcriptome analysis revealed that subinhibitory concentrations of azithromycin reduced the expression of genes involved in stress-induced mutagenesis, including the stress response sigma factor .

Identification of the Pseudomonas aeruginosa AgtR-CspC-RsaL pathway that controls Las quorum sensing in response to metabolic perturbation and Staphylococcus aureus.

Environmental metabolites and metabolic pathways significantly influence bacterial pathogenesis and interspecies competition. We previously discovered that a mutation in the triosephosphate isomerase gene, tpiA, in Pseudomonas aeruginosa led to defective type III secretion and increased susceptibility to aminoglycoside antibiotics. In this study, we found that the tpiA mutation enhances the Las quorum sensing system due to reduced translation of the negative regulator RsaL.

Synthesis and Evaluation of Melittin-Modified Peptides for Antibacterial Activity.

Melittin, a naturally occurring antimicrobial peptide, demonstrates broad-spectrum activity, effectively suppressing and eliminating both Gram-positive and Gram-negative bacteria, including specific drug-resistant strains. In this study, molecular simulation software was employed to investigate and modify the structure of melittin with the aim of synthesizing a modified peptide exhibiting enhanced antibacterial potency and assessing its bacteriostatic and antibacterial properties. The primary research objectives were as follows: 1.

Pseudomonas aeruginosa-derived DnaJ induces TLR2 expression through TLR10-mediated activation of the PI3K-SGK1 pathway in macrophages.

TLR2 is a key component of the innate immune system, responsible for recognizing Gram-positive bacterial components and initiating inflammatory signaling cascades that activate defense responses. However, little is known about the regulatory effects of Pseudomonas aeruginosa (P. aeruginosa) on TLR2 expression.

Regulation of Bone Remodeling by Metal-Phenolic Networks for the Treatment of Systemic Osteoporosis.

Osteoporosis is a systemic metabolic disease that impairs bone remodeling by favoring osteoclastic resorption over osteoblastic formation. Nanotechnology-based therapeutic strategies focus on the delivery of drug molecules to either decrease bone resorption or increase bone formation rather than regulating the entire bone remodeling process, and osteoporosis interventions suffer from this limitation. Here, we present a multifunctional nanoparticle based on metal-phenolic networks (MPNs) for the treatment of systemic osteoporosis by regulating both osteoclasts and osteoblasts.

Bismuth-based drugs sensitize Pseudomonas aeruginosa to multiple antibiotics by disrupting iron homeostasis.

Pseudomonas aeruginosa infections are difficult to treat due to rapid development of antibiotic drug resistance. The synergistic combination of already-in-use drugs is an alternative to developing new antibiotics to combat antibiotic-resistant bacteria. Here we demonstrate that bismuth-based drugs (bismuth subsalicylate, colloidal bismuth subcitrate) in combination with different classes of antibiotics (tetracyclines, macrolides, quinolones, rifamycins and so on) can eliminate multidrug-resistant P.

Host Cells Upregulate Phosphate Transporter PIT1 to Inhibit Intracellular Growth.

infects and proliferates inside monocytes or macrophages and causes human monocytic ehrlichiosis (HME), an emerging life-threatening tick-borne zoonosis. After internalization, resides in specialized membrane-bound inclusions, -containing vesicles (ECVs), to evade from host cell innate immune responses and obtain nutrients. However, mechanisms exploited by host cells to inhibit growth in ECVs are still largely unknown.

An Amphiphilic Surface with Improved Thermal Radiation for Water Harvesting.

Water scarcity poses a significant challenge for people living in arid areas. Despite the effectiveness of many bioinspired surfaces in promoting vapor condensation, their water-harvesting efficiency is insufficient. This is often exacerbated by overheating, which decreases the performance in terms of the micro-droplet concentration and movement on surfaces.

Using host-mimicking conditions and a murine cutaneous abscess model to identify synergistic antibiotic combinations effective against .

Antibiotic drug combination therapy is critical for the successful treatment of infections caused by multidrug resistant pathogens. We investigated the efficacy of β-lactam and β-lactam/β-lactamase inhibitor combinations with other antibiotics, against the hypervirulent, ceftazidime/avibactam resistant Liverpool epidemic strain (LES) B58. Although minimum inhibitory concentrations differed by up to eighty-fold between standard and host-mimicking media, combinatorial effects only marginally changed between conditions for some combinations.

Janus liposozyme for the modulation of redox and immune homeostasis in infected diabetic wounds.

Diabetic foot ulcers often become infected, leading to treatment complications and increased risk of loss of limb. Therapeutics to manage infection and simultaneously promote healing are needed. Here we report on the development of a Janus liposozyme that treats infections and promotes wound closure and re-epithelialization.

Fluorinated Organic Polymers for Cancer Drug Delivery.

In the realm of cancer therapy, the spotlight is on nanoscale pharmaceutical delivery systems, especially polymer-based nanoparticles, for their enhanced drug dissolution, extended presence in the bloodstream, and precision targeting achieved via surface engineering. Leveraging the amplified permeation and retention phenomenon, these systems concentrate therapeutic agents within tumor tissues. Nonetheless, the hurdles of systemic toxicity, biological barriers, and compatibility with living systems persist.

Enhancing bactericidal activities of ciprofloxacin by targeting the trans-translation system that is involved in stress responses in Klebsiella pneumoniae.

Although the trans-translation system is a promising target for antcibiotic development, its antibacterial mechanism in Klebsiella pneumoniae (KP) is unclear. Considering that tmRNA was the core component of trans-translation, this study firstly investigated phenotypic changes caused by various environmental stresses in KP lacking trans-translation activities (tmRNA-deleted), and then aimed to evaluate antibacterial activities of the trans-translation-targeting antibiotic combination (tobramycin/ciprofloxacin) in clinical KP isolates based on inhibition activities of aminoglycosides against trans-translation. We found that the tmRNA-deleted strain P4325/ΔssrA was significantly more susceptible than the wild-type KP strain P4325 under environments with hypertonicity (0.

Etf-3 Induces Host Upregulation for Bacterial Intracellular Growth.

infects human monocytes or macrophages and causes human monocytic ehrlichiosis (HME), an emerging life-threatening zoonosis. After internalization, resides in membrane-bound inclusions, -containing vesicles (ECVs), which have early endosome-like characteristics and fuse with early autophagosomes but not lysosomes, to evade host innate immune microbicidal mechanisms and obtain nutrients for bacterial intracellular growth. The mechanisms exploited by to modulate intracellular vesicle trafficking in host cells have not been comprehensively studied.

Murepavadin promotes the killing efficacies of aminoglycoside antibiotics against by enhancing membrane potential.

Murepavadin is a peptidomimetic that specifically targets the lipopolysaccharide transport protein LptD of . Here, we found that murepavadin enhances the bactericidal efficacies of tobramycin and amikacin. We further demonstrated that murepavadin enhances bacterial respiration activity and subsequent membrane potential, which promotes intracellular uptake of aminoglycoside antibiotics.

MvaT binds to the P promoter to repress the type III secretion system in .

is an opportunistic human pathogen capable of causing a variety of acute and chronic infections. Its type III secretion system (T3SS) plays a critical role in pathogenesis during acute infection. ExsA is a master regulator that activates the expression of all T3SS genes.

Network pharmacology and experimental validation methods to reveal the active compounds and hub targets of Curculigo orchioides Gaertn in rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is an autoimmune disease that can lead to joint destruction and deformity. Curculigo orchioides Gaertn (CO) was previously revealed to play a significant role in RA treatment. However, the main active ingredients and molecular mechanisms of CO in regulating RA are still unclear.

Murepavadin induces envelope stress response and enhances the killing efficacies of β-lactam antibiotics by impairing the outer membrane integrity of .

is a ubiquitous opportunistic pathogen that can cause a variety of acute and chronic infections. The bacterium is highly resistant to numerous antibiotics. Murepavadin is a peptidomimetic antibiotic that blocks the function of lipopolysaccharide (LPS) transport protein D (LptD), thus inhibiting the insertion of LPS into the outer membrane.

PitA Controls the H2- and H3-T6SSs through PhoB in Pseudomonas aeruginosa.

Pseudomonas aeruginosa possesses three type VI secretion systems (T6SSs) that are involved in interspecies competition, internalization into epithelial cells, and virulence. Host-derived mucin glycans regulate the T6SSs through RetS, and attacks from other species activate the H1-T6SS. However, other environmental signals that control the T6SSs remain to be explored.

MvfR Controls Tolerance to Polymyxin B by Regulating in Pseudomonas aeruginosa.

Polymyxins are currently the last-resort antibiotics for the treatment of multidrug-resistant Gram-negative bacterial infections. To expand the understanding of the intrinsic resistance mechanism against polymyxins, a laboratory strain of Pseudomonas aeruginosa PAO1 was subjected to serial passage in the presence of sublethal doses of polymyxin B over a period of 30 days. By whole-genome sequencing of successively isolated polymyxin B-resistant isolates, we identified a frameshift mutation (L183fs) in the gene that further increased polymyxin resistance in the mutant background.